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Squamous cell carcinoma of the cervix metastatic to the skin
Squamous cell carcinoma of the cervix metastatic to the skin Mark H. Kagen, MD,a Kimberly K. Ruhl, MD, PhD,b Carol Aghajanian, MD,c and Patricia L. Myskowski, MDd New York, New York Carcinoma of the cervix is a common neoplasm, which annually affects 50,000 women in the United States. When cervical carcinoma metastasizes, it most often involves the lung, bone, and liver; only rarely does it metastasize to the skin. We describe a patient with previously diagnosed carcinoma of the cervix who presented with a lesion on the lateral aspect of her left leg. (J Am Acad Dermatol 2001;45:133-5.)
C
arcinoma of the cervix is a common neoplasm, annually affecting 50,000 women in the United States.1 Early detection programs through Papanicolaou tests often diagnose the disease in early stages, but invasive and metastatic diseases do occur. When carcinoma of the cervix does metastasize, it most often involves the lung, bone, and liver. Skin metastases are very rare, with a quoted incidence ranging from 0.7% to 4.4%.2-6 We describe a patient with previously diagnosed carcinoma of the cervix, who presented with an unusual cutaneous metastasis.
CASE REPORT A 43-year-old white woman was in good health until March 1995, when vaginal bleeding developed. A Papanicolaou smear was reportedly negative in May, but results of a cone biopsy in July revealed malignant cells. In October she underwent exploratory laparotomy with pelvic lymph node dissection and radical hysterectomy for stage IB cervical carcinoma. Histopathologic examination revealed invasive squamous cell carcinoma of the uterine cervix (Fig 1). The tumor was large cell, nonkeratinizing, and poorly differentiated with an exophytic growth pattern and a maximal
From the Laboratory for Investigative Dermatology, Rockefeller Universitya; the Department of Dermatology, The New York–Presbyterian Hospital, Cornell Medical Centerb; and Developmental Chemotherapy Servicec and the Dermatology Service,d Memorial-Sloan Kettering Hospital. Presented at the 56th Annual Meeting of the American Academy of Dermatology, Orlando, Fla, Feb 27-March 4, 1998. Reprint requests: Patricia L. Myskowski, Dermatology Service, Memorial-Sloan Kettering Hospital, 1275 York Ave, New York, NY 10021. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/91/112389 doi:10.1067/mjd.2001.112389
Fig 1. Histopathologic findings of the cervix (October 1995) revealing large-cell, nonkeratinizing, poorly differentiated squamous cell carcinoma.
thickness of cervical stromal invasion of 10 mm. Metastatic carcinoma was found in 1 in 10 right external iliac nodes and 1 in 5 left hypogastric lymph nodes. She declined postoperative chemotherapy or radiation therapy. 133
134 Kagen et al
Fig 2. Plaque on patient’s left thigh (July 1996).
In March 1996, a venous thrombosis developed in the left lower extremity. Pelvic ultrasound indicated cystic lesions in the pelvis with biopsy-confirming metastatic cervical carcinoma. The patient received external radiation therapy of the pelvis, followed by chemotherapy with cisplatin and 5-fluorouracil. In July 1996 she was also found to have metastases to the liver and lungs. Subsequently during that same month, she presented to the Dermatology Service with complaints of a left lateral thigh lesion, which she reported had been present for about 6 weeks, accompanied by fever up to 39.7°C. She had undergone a 10-day course of oral cephalexin for presumed infection with minimal improvement. Physical examination revealed a 5-cm, round, firm, indurated, erythematous plaque on the left lateral upper thigh (Fig 2). The plaque was ulcerated with undermined borders and with a whitish exudate. It was tender and warm to the touch. The left thigh was also noted to be edematous. Biopsy findings of the plaque revealed metastatic squamous cell carcinoma, poorly differentiated,
J AM ACAD DERMATOL JULY 2001
Fig 3. Photomicrograph of biopsy specimen from plaque revealing large-cell, nonkeratinizing, poorly differentiated squamous cell carcinoma, consistent with the patient’s primary tumor.
large-cell type, nonkeratinizing, and consistent with the patient’s primary tumor (Fig 3). Chemotherapy was switched to ifosfamide and mesna, but the patient had progressive disease and died of pulmonary complications 3 months later.
DISCUSSION Carcinoma of the cervix is the fourth most common malignant neoplasm in women. More than 90% of patients have disease that is confined to the pelvis, and those that metastasize do so most commonly to lung, liver, and bone.7 Cutaneous manifestations are distinctly rare. Cutaneous metastases from solid tumors affect 0.7% to 9.0% of patients with solid tumors and usually are associated with advanced disease.8 They usually fall into 1 of 3 main forms: nodules, plaques, or inflammatory telangiectatic lesions. Among these types, nodules are the most common.9 The size of lesions reported in the literature has ranged from 5 to 80 mm; most lesions are smaller than 30 mm in diameter.2 The involved skin is fre-
J AM ACAD DERMATOL VOLUME 45, NUMBER 1
quently warm, tender, edematous, and erythematous, mimicking cellulitis.3 The mechanisms involved in metastasis can be viewed as a sequence of steps: first, detachment from the primary tumor, then invasion, intravasation into a blood or lymphatic vessel, extravasation, invasion into tissue, and proliferation at the metastatic site.8 Factors that have been postulated in determining the proclivity of tumors to metastasize and site of metastasis include the oxygen tension of the primary tumor10 and body segmental temperature,11 respectively. The most common sites of cutaneous metastasis of cervical carcinoma are the abdominal wall and vulva, followed by anterior chest wall and upper and lower extremities.2 This pattern may reflect the tendency of cutaneous metastases to appear near the site of the primary tumor and suggests that the usual mode of spread of metastases is thought to be through local dermal lymphatic channels.12 Cutaneous metastases at more distal sites may travel hematogenously. The incidence of metastasis to the skin is also dependent on the cell type. Undifferentiated carcinomas have a 20% incidence of metastasis followed by adenocarcinoma (5.8%) and squamous cell carcinoma (0.9%.)2 Prognosis is generally poor in patients with cutaneous metastases and is often perceived as a preterminal event, generally occurring in the later stages of illness. Survival is usually measured in months, with a range of 1 to 37 months (average, 8.5 months) after diagnosis of the cutaneous metastasis.4 Treatment of the skin is palliative and may consist of local irradiation, surgical excision, or chemotherapy.5,6 Of note, our patient presented with a cutaneous metastasis that was unusual in several respects. First was the location on the lower extremity. Furthermore, clinical presentation was atypical in that the lesion was ulcerated, and this is quite unusual in cutaneous metastases. The lesion was also fairly large (5 cm) compared with most cutaneous metas-
Kagen et al 135
tases. The differential diagnosis included pyoderma gangrenosum and bacterial abscess. Finally, the cell type in this case was squamous cell carcinoma, which rarely metastasizes to the skin, when compared with adenocarcinoma. In our patient a cutaneous lesion developed 11 months after the diagnosis of cervical carcinoma, which is comparable with the reported mean of 16.9 months.2 In summary, our report correlates with previous ones regarding the ominous prognosis that a cutaneous metastasis can imply, with death occurring within 3 months of presentation in this case. REFERENCES 1. Schoell WM, Janicek MF, Mirhashemi R. Epidemiology and biology of cervical cancer. Semin Surg Oncol 1999;16:203-11. 2. Imachi M, Tsukamoto N, Kinoshita S, Nakano H. Skin metastasis from carcinoma of the uterine cervix. Gynecol Oncol 1993;48:349-54. 3. Freeman C, Rozenfeld M, Scholplacher P. Cutaneous metastases from carcinoma of the cervix. Arch Dermatol 1982;118:40-1. 4. Copas PR, Spann CO, Thoms WW, Horowitz IR. Squamous cell carcinoma of the cervix metastatic to a drain site. Gynecol Oncol 1995;56:102-4. 5. Tharakaram S, Rajendran SS, Premalatha S, Yesudian PZ. Cutaneous metastasis from carcinoma cervix. Int J Dermatol 1985;24:598-9. 6. Hayes A, Berry A. Cutaneous metastasis from squamous cell carcinoma of the cervix. J Am Acad Dermatol 1992;26:846-50. 7. Brownstein M, Helwig E. Patterns of cutaneous metastasis. Arch Dermatol 1972;105:862-8. 8. Schwartz RA. Cutaneous metastatic disease. J Am Acad Dermatol 1995;33:161-82. 9. Brownstein M, Helwig E. Spread of tumors to the skin. Arch Dermatol 1973;107:80-6. 10. Sundfor K, Lyng H, Rofstad EK. Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 1998;78:822-7. 11. Fay T, Henry GC. Correlation of body segmental temperature and its relation to the location of carcinomatous metastasis: clinical observations and response to methods of refrigeration. Surg Gynecol Obstet 1938;66:512-24. 12. Bordin G, Wetzner S. Cutaneous metastases as a manifestation of internal carcinoma: diagnostic and prognostic significance. Am Surg 1972;38:629-34.
C
arcinoma of the cervix is a common neoplasm, annually affecting 50,000 women in the United States.1 Early detection programs through Papanicolaou tests often diagnose the disease in early stages, but invasive and metastatic diseases do occur. When carcinoma of the cervix does metastasize, it most often involves the lung, bone, and liver. Skin metastases are very rare, with a quoted incidence ranging from 0.7% to 4.4%.2-6 We describe a patient with previously diagnosed carcinoma of the cervix, who presented with an unusual cutaneous metastasis.
CASE REPORT A 43-year-old white woman was in good health until March 1995, when vaginal bleeding developed. A Papanicolaou smear was reportedly negative in May, but results of a cone biopsy in July revealed malignant cells. In October she underwent exploratory laparotomy with pelvic lymph node dissection and radical hysterectomy for stage IB cervical carcinoma. Histopathologic examination revealed invasive squamous cell carcinoma of the uterine cervix (Fig 1). The tumor was large cell, nonkeratinizing, and poorly differentiated with an exophytic growth pattern and a maximal
From the Laboratory for Investigative Dermatology, Rockefeller Universitya; the Department of Dermatology, The New York–Presbyterian Hospital, Cornell Medical Centerb; and Developmental Chemotherapy Servicec and the Dermatology Service,d Memorial-Sloan Kettering Hospital. Presented at the 56th Annual Meeting of the American Academy of Dermatology, Orlando, Fla, Feb 27-March 4, 1998. Reprint requests: Patricia L. Myskowski, Dermatology Service, Memorial-Sloan Kettering Hospital, 1275 York Ave, New York, NY 10021. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/91/112389 doi:10.1067/mjd.2001.112389
Fig 1. Histopathologic findings of the cervix (October 1995) revealing large-cell, nonkeratinizing, poorly differentiated squamous cell carcinoma.
thickness of cervical stromal invasion of 10 mm. Metastatic carcinoma was found in 1 in 10 right external iliac nodes and 1 in 5 left hypogastric lymph nodes. She declined postoperative chemotherapy or radiation therapy. 133
134 Kagen et al
Fig 2. Plaque on patient’s left thigh (July 1996).
In March 1996, a venous thrombosis developed in the left lower extremity. Pelvic ultrasound indicated cystic lesions in the pelvis with biopsy-confirming metastatic cervical carcinoma. The patient received external radiation therapy of the pelvis, followed by chemotherapy with cisplatin and 5-fluorouracil. In July 1996 she was also found to have metastases to the liver and lungs. Subsequently during that same month, she presented to the Dermatology Service with complaints of a left lateral thigh lesion, which she reported had been present for about 6 weeks, accompanied by fever up to 39.7°C. She had undergone a 10-day course of oral cephalexin for presumed infection with minimal improvement. Physical examination revealed a 5-cm, round, firm, indurated, erythematous plaque on the left lateral upper thigh (Fig 2). The plaque was ulcerated with undermined borders and with a whitish exudate. It was tender and warm to the touch. The left thigh was also noted to be edematous. Biopsy findings of the plaque revealed metastatic squamous cell carcinoma, poorly differentiated,
J AM ACAD DERMATOL JULY 2001
Fig 3. Photomicrograph of biopsy specimen from plaque revealing large-cell, nonkeratinizing, poorly differentiated squamous cell carcinoma, consistent with the patient’s primary tumor.
large-cell type, nonkeratinizing, and consistent with the patient’s primary tumor (Fig 3). Chemotherapy was switched to ifosfamide and mesna, but the patient had progressive disease and died of pulmonary complications 3 months later.
DISCUSSION Carcinoma of the cervix is the fourth most common malignant neoplasm in women. More than 90% of patients have disease that is confined to the pelvis, and those that metastasize do so most commonly to lung, liver, and bone.7 Cutaneous manifestations are distinctly rare. Cutaneous metastases from solid tumors affect 0.7% to 9.0% of patients with solid tumors and usually are associated with advanced disease.8 They usually fall into 1 of 3 main forms: nodules, plaques, or inflammatory telangiectatic lesions. Among these types, nodules are the most common.9 The size of lesions reported in the literature has ranged from 5 to 80 mm; most lesions are smaller than 30 mm in diameter.2 The involved skin is fre-
J AM ACAD DERMATOL VOLUME 45, NUMBER 1
quently warm, tender, edematous, and erythematous, mimicking cellulitis.3 The mechanisms involved in metastasis can be viewed as a sequence of steps: first, detachment from the primary tumor, then invasion, intravasation into a blood or lymphatic vessel, extravasation, invasion into tissue, and proliferation at the metastatic site.8 Factors that have been postulated in determining the proclivity of tumors to metastasize and site of metastasis include the oxygen tension of the primary tumor10 and body segmental temperature,11 respectively. The most common sites of cutaneous metastasis of cervical carcinoma are the abdominal wall and vulva, followed by anterior chest wall and upper and lower extremities.2 This pattern may reflect the tendency of cutaneous metastases to appear near the site of the primary tumor and suggests that the usual mode of spread of metastases is thought to be through local dermal lymphatic channels.12 Cutaneous metastases at more distal sites may travel hematogenously. The incidence of metastasis to the skin is also dependent on the cell type. Undifferentiated carcinomas have a 20% incidence of metastasis followed by adenocarcinoma (5.8%) and squamous cell carcinoma (0.9%.)2 Prognosis is generally poor in patients with cutaneous metastases and is often perceived as a preterminal event, generally occurring in the later stages of illness. Survival is usually measured in months, with a range of 1 to 37 months (average, 8.5 months) after diagnosis of the cutaneous metastasis.4 Treatment of the skin is palliative and may consist of local irradiation, surgical excision, or chemotherapy.5,6 Of note, our patient presented with a cutaneous metastasis that was unusual in several respects. First was the location on the lower extremity. Furthermore, clinical presentation was atypical in that the lesion was ulcerated, and this is quite unusual in cutaneous metastases. The lesion was also fairly large (5 cm) compared with most cutaneous metas-
Kagen et al 135
tases. The differential diagnosis included pyoderma gangrenosum and bacterial abscess. Finally, the cell type in this case was squamous cell carcinoma, which rarely metastasizes to the skin, when compared with adenocarcinoma. In our patient a cutaneous lesion developed 11 months after the diagnosis of cervical carcinoma, which is comparable with the reported mean of 16.9 months.2 In summary, our report correlates with previous ones regarding the ominous prognosis that a cutaneous metastasis can imply, with death occurring within 3 months of presentation in this case. REFERENCES 1. Schoell WM, Janicek MF, Mirhashemi R. Epidemiology and biology of cervical cancer. Semin Surg Oncol 1999;16:203-11. 2. Imachi M, Tsukamoto N, Kinoshita S, Nakano H. Skin metastasis from carcinoma of the uterine cervix. Gynecol Oncol 1993;48:349-54. 3. Freeman C, Rozenfeld M, Scholplacher P. Cutaneous metastases from carcinoma of the cervix. Arch Dermatol 1982;118:40-1. 4. Copas PR, Spann CO, Thoms WW, Horowitz IR. Squamous cell carcinoma of the cervix metastatic to a drain site. Gynecol Oncol 1995;56:102-4. 5. Tharakaram S, Rajendran SS, Premalatha S, Yesudian PZ. Cutaneous metastasis from carcinoma cervix. Int J Dermatol 1985;24:598-9. 6. Hayes A, Berry A. Cutaneous metastasis from squamous cell carcinoma of the cervix. J Am Acad Dermatol 1992;26:846-50. 7. Brownstein M, Helwig E. Patterns of cutaneous metastasis. Arch Dermatol 1972;105:862-8. 8. Schwartz RA. Cutaneous metastatic disease. J Am Acad Dermatol 1995;33:161-82. 9. Brownstein M, Helwig E. Spread of tumors to the skin. Arch Dermatol 1973;107:80-6. 10. Sundfor K, Lyng H, Rofstad EK. Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 1998;78:822-7. 11. Fay T, Henry GC. Correlation of body segmental temperature and its relation to the location of carcinomatous metastasis: clinical observations and response to methods of refrigeration. Surg Gynecol Obstet 1938;66:512-24. 12. Bordin G, Wetzner S. Cutaneous metastases as a manifestation of internal carcinoma: diagnostic and prognostic significance. Am Surg 1972;38:629-34.